1. San Antonio Breast Cancer Symposium 2012 Helen K. Chew, MD, FACP Professor of Medicine

2. Objectives 1.Adjuvant tamoxifen duration (S1-2) 2.Adjuvant trastuzumab duration (S5-2) 3.Adjuvant chemotherapy for isolated local regional recurrence (S3-2) 4.Role of bevacizumab? (S1-7, S6-5)

4. Figure 5 Effects of about 5 years of tamoxifen on the 15-year probabilities of recurrence and of breast cancer mortality, for ER- positive disease Outcome by allocated treatment in trials of about 5 years of adjuvant tamoxifen. Event rate ratio (... Early Breast Cancer Trialists' Collaborative Group (EBCTCG) Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: patient-level meta- analysis of randomised trials The Lancet Volume 378, Issue 9793 2011 771 - 784 http://dx.doi.org/10.1016/S0140-6736(11)60993-8

6. ATLAS Very large, pragmatic study (1996-2005) No restrictions on age, hormone receptor status, nodal status or other treatments No protocol-defined visits or evaluations except for yearly MD questionnaire Protocol amended in 2000 when 5 years of tamoxifen was superior to 2 years Published online Lancet 12/5/12

7. Table 1, ER+ tumors Tamoxifen x 5 years n=3418 Tamoxifen x 10 years N=3428 Age, years% <451819 45-5432 55-6940 >70109 Nodal status% N05453 1-3 nodes2627 >4 nodes16 Tumor size% T14748 T23938 T377 Menopausal status% Premenopausal910 Postmenopausal89

10. Figure 3 Recurrence (A) and breast cancer mortality (B) by treatment allocation for 6846 women with ER-positive disease Bars show SE. Recurrence rates are percentage per year (events/patient-years of follow-up). Death rates (overall rate???rate... Christina Davies, Hongchao Pan, Jon Godwin, Richard Gray, Rodrigo Arriagada, Vinod Raina, Mirta Abraham, V... Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer: ATLAS, a randomised trial The Lancet null 2012 null http://dx.doi.org/10.1016/S0140-6736(12)61963-1

11. Figure 2 Treatment compliance (A) and proportion of patients in follow-up (B) by year since randomisation for 6846 women with ER- positive disease (54% node-negative) *>99% tamoxifen. Christina Davies, Hongchao Pan, Jon Godwin, Richard Gray, Rodrigo Arriagada, Vinod Raina, Mirta Abraham, V... Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer: ATLAS, a randomised trial The Lancet null 2012 null http://dx.doi.org/10.1016/S0140-6736(12)61963-1

14. How does this impact clinical care? For patients who are appropriate candidates for tamoxifen therapy, 10 years of tamoxifen is recommended. This trial cannot be compared to any strategies that have incorporated aromatase inhibitors.

27. How does this impact clinical care? One year of adjuvant trastuzumab remains the standard of care. PHARE trial (abstract #S5-3) was a subset analysis of non-inferiority of 6 versus 12 months of adjuvant trastuzumab.

45. How does this impact clinical care? A course of adjuvant chemotherapy after an isolated local regional recurrence improves DFS and OS. The benefits appear less convincing for hormone receptor positive disease. Sites of recurrence (ipsilateral breast versus chest wall) and timing of recurrence and their correlation with outcomes were not reported in detail.

64. How does this impact clinical care? The addition of bevacizumab to first-line endocrine therapy in hormone-receptor positive MBC did not improve PFS. This addition of bevacizumab to first-line chemotherapy for early stage triple negative breast cancer did not improve DFS. The role of bevacizumab in breast cancer is not well defined and bevacizumab should not be used outside of a clinical trial.

65. Thank you. Questions?